MYH9 Promotes Growth and Metastasis via Activation of MAPK/AKT Signaling in Colorectal Cancer
MYH9 Promotes Growth and Metastasis via Activation of MAPK/AKT Signaling in Colorectal Cancer
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MYH9 通过激活结直肠癌中的 MAPK/AKT 信号传导促进生长和转移
DOI：
10.7150/jca.27635
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发表时间：
2019-01-01
影响因子：
3.9
通讯作者：
Li, Guoxin
中科院分区：
文献类型：
--
作者：
Wang, Bin;Qi, Xiaolong;Li, Guoxin
收缩蛋白Myh9(非肌肉肌球蛋白IIA)是一种肌动蛋白结合蛋白，在细胞黏附、迁移和分裂中发挥重要作用。然而，它在结直肠癌(CRC)中的独特作用仍不清楚。在这项研究中，我们用免疫印迹和组织芯片免疫组织化学(IHC)检测到在结直肠癌组织和配对的正常组织中有显著的Myh9过表达。此外，对患者临床资料的分析表明，Myh9的过度表达与淋巴结转移和总体生存不良密切相关。内源性Myh9过表达增强了细胞的体外增殖和迁移能力，促进了小鼠结直肠癌的生长。Myh9的沉默在体外和体内都显示了对大肠癌细胞的抑制作用。此外，涉及MAPK/AKT信号转导的上皮-间充质转化(EMT)的主要生物力学揭示了Myh9依赖的细胞行为。总之，我们的数据显示，Myh9通过调节MAPK/AKT信号显著促进肿瘤的发生，并与结直肠癌的不良预后显著相关。因此，Myh9可能成为诊断和治疗结直肠癌的一种新的生物标志物和药物靶点。
The contractile protein MYH9 (non-muscle myosin IIA) is an actin-binding protein that plays a fundamental role in cell adhesion, migration, and division. However, its distinct role in colorectal cancer (CRC) still remains unidentified. In this study, we detected significant MYH9 overexpression in CRC samples compared with paired normal tissues using western blotting and tissue microarray immunohistochemistry (IHC). Moreover, analysis of patient clinical information demonstrated that MYH9 overexpression was strongly correlated with lymph node metastasis and poor overall survival. Endogenous overexpression of MYH9 enhanced the ability of cell proliferation and migration in vitro, and accelerated CRC growth in mouse models. Silencing of MYH9 revealed repressive effects on CRC cells in vitro and in vivo. Furthermore, primary biomechanics that involved MAPK/AKT signaling mediated epithelial-mesenchymal transition (EMT) was uncovered underlying MYH9 dependent cell behaviors. Collectively, our data showed that MYH9 significantly promoted tumorigenesis by regulating MAPK/AKT signaling, and was remarkably correlated with poor prognosis in CRC. MYH9 may thus be a novel biomarker and drug target in the diagnosis and treatment of CRC.